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(searched for: doi:10.3816/clml.2011.n.001)
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, Gordon H. Guyatt, Trevor Teich, Jamie L. Dawdy, Shaneela Shahid, Jessica K. Altman, Richard M. Stone, Mikkael A. Sekeres, Sudipto Mukherjee, Thomas W. LeBlanc, et al.
Published: 30 March 2021
PLoS ONE, Volume 16; doi:10.1371/journal.pone.0249087

Abstract:
To compare the effectiveness and safety of intensive antileukemic therapy to less-intensive therapy in older adults with acute myeloid leukemia (AML) and intermediate or adverse cytogenetics, we searched the literature in Medline, Embase, and CENTRAL to identify relevant studies through July 2020. We reported the pooled hazard ratios (HRs), risk ratios (RRs), mean difference (MD) and their 95% confidence intervals (CIs) using random-effects meta-analyses and the certainty of evidence using the GRADE approach. Two randomized trials enrolling 529 patients and 23 observational studies enrolling 7296 patients proved eligible. The most common intensive interventions included cytarabine-based intensive chemotherapy, combination of cytarabine and anthracycline, or daunorubicin/idarubicin, and cytarabine plus idarubicin. The most common less-intensive therapies included low-dose cytarabine alone, or combined with clofarabine, azacitidine, and hypomethylating agent-based chemotherapy. Low certainty evidence suggests that patients who receive intensive versus less-intensive therapy may experience longer survival (HR 0.87; 95% CI, 0.76–0.99), a higher probability of receiving allogeneic hematopoietic stem cell transplantation (RR 6.14; 95% CI, 4.03–9.35), fewer episodes of pneumonia (RR, 0.25; 95% CI, 0.06–0.98), but a greater number of severe, treatment-emergent adverse events (RR, 1.34; 95% CI, 1.03–1.75), and a longer duration of intensive care unit hospitalization (MD, 6.84 days longer; 95% CI, 3.44 days longer to 10.24 days longer, very low certainty evidence). Low certainty evidence due to confounding in observational studies suggest superior overall survival without substantial treatment-emergent adverse effect of intensive antileukemic therapy over less-intensive therapy in older adults with AML who are candidates for intensive antileukemic therapy.
, Alessandra Picardi
Published: 22 January 2020
Expert Review of Hematology, Volume 13, pp 99-108; doi:10.1080/17474086.2020.1715207

The publisher has not yet granted permission to display this abstract.
Pharmacogenomics and Personalized Medicine, pp 169-181; doi:10.2147/PGPM.S105208

Abstract:
ABCB1 genetic variants in leukemias: current insights into treatment outcomes Ravindran Ankathil Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia Despite improvements in treatment of different types of leukemia, not all patients respond optimally for a particular treatment. Some treatments will work better for some, while being harmful or ineffective for others. This is due to genetic variation in the form of single-nucleotide polymorphisms (SNPs) that affect gene expression or function and cause inherited interindividual differences in the metabolism and disposition of drugs. Drug transporters are one of the determinants governing the pharmacokinetic profile of chemotherapeutic drugs. The ABCB1 transporter gene transports a wide range of drugs, including drugs used in leukemia treatment. Polymorphisms in the ABCB1 gene do affect intrinsic resistance and pharmacokinetics of several drugs used in leukemia treatment protocols and thereby affect the efficacy of treatment and event-free survival. This review focuses on the impact of three commonly occurring SNPs (1236C>T, 2677G>T/A, and 3435C>T) of ABCB1 on treatment response of various types of leukemia. From the literature available, some of the genotypes and haplotypes of these SNPs have been found to be potential determinants of interindividual variability in drug disposition and pharmacologic response in different types of leukemia. However, due to inconsistencies in the results observed across the studies, additional studies, considering novel genomic methodologies, comprehensive definition of clinical phenotypes, adequate sample size, and uniformity in all the confounding factors, are warranted. Keywords: leukemia, ABCB1 polymorphisms, chemotherapy response, survival
, Paola Carluccio, Caterina Buquicchio, Carolina Vergine, Giuseppina Greco, Barbara Amurri, Angela Melpignano, Lorella Melillo, Nicola Cascavilla, Attilio Guarini, et al.
Published: 1 November 2015
Leukemia Research, Volume 39, pp 1166-1171; doi:10.1016/j.leukres.2015.08.005

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, Renata Maceu Salhab, Viviana Giampaoli, , Maria De Lourdes Chauffaille
Revista Brasileira de Hematologia e Hemoterapia, Volume 37, pp 109-14; doi:10.1016/j.bjhh.2015.02.003

Abstract:
Myeloid neoplasms are heterogeneous diseases that are more incident in the elderly. The goals of this study were to aggregate a geriatric approach to the patient assessment, to show the impact of gender, age, hemoglobin concentration and comorbidities on the functionality of elderly with myeloid neoplasms and to better understand how the instruments of functional assessment work according to the aggressiveness of the disease. Elderly patients (≥60 years old) with myeloid neoplasms were assessed using the Karnofsky scale, Eastern Cooperative Oncologic Group scale, and basic and instrumental activities of daily living scales. The hematopoietic cell transplantation-comorbidity index assessed the comorbidities. A mixed logistical regression model was fitted to estimate the impact of gender, age, hemoglobin concentration and the hematopoietic cell transplantation-comorbidity index on patients' functionality. Eighty-two patients with a mean age of 72.8 years (range: 60-92 years) were evaluated. Eighty percent had good Karnofsky and Eastern Cooperative Oncologic Group scales and 39% were independent according to the daily living activity scales. All of the patients with poor Karnofsky and Eastern Cooperative Oncologic Group scales were classified as dependent by the daily living activity scales. The mixed logistic regression models showed that age, gender, hemoglobin concentration and the comorbidity index impacted on the daily living activity scales. Karnofsky and Eastern Cooperative Oncologic Group scales were affected by hemoglobin and the comorbidity index. The model hypothesized the hemoglobin concentration at which there was a higher risk of poor Karnofsky and Eastern Cooperative Oncologic Group scales. This hemoglobin concentration depended on comorbidities and on the aggressiveness of the myeloid neoplasm. The geriatric approach improved the sensitivity and specificity of the patients' assessment. Hemoglobin concentration associated to the risk of poor Karnofsky and Eastern Cooperative Oncologic Group scales depended on the comorbidity score and on the disease aggressiveness. The Karnofsky and Eastern Cooperative Oncologic Group scales had higher sensitivity in patients with more aggressive diseases.
Imit Kaur, Jonathan E Constance, Ken M Kosak, ,
Expert Opinion on Drug Metabolism & Toxicology, Volume 11, pp 53-65; doi:10.1517/17425255.2015.972934

The publisher has not yet granted permission to display this abstract.
Jiadai Xu, Tingmei Chen, Yun Liu, Huayuan Zhu, Wei Wu, Wenyi Shen, Bei Xu, Sixuan Qian, Jianyong Li,
The Journal of Biomedical Research, Volume 28, pp 396-405; doi:10.7555/jbr.28.20130164

Abstract:
We retrospectively investigated the prognostic factors of acute myeloid leukemia (AML) in 152 Chinese patients with de novo AML who were older than 60 years of age and who received treatment at our hospital. Log-rank test showed that 6 parameters including older age, higher white blood cell (WBC) counts, lactate dehydrogenase (LDH) and bone marrow (BM) blasts at diagnosis, unfavorable risk cytogenetics, and non-mutated CEBPα were significant adverse prognostic factors of overall survival (OS) for elderly AML patients (P = 0.0013, 0.0358, 0.0132, 0.0242, 0.0236 and 0.0130, respectively). Moreover, older age and higher LDH were significant adverse predictors for relapse-free survival (RFS) (P = 0.0447 and 0.0470, respectively). Univariate analysis revealed similar results for OS to those of the log-rank test and only higher LDH at diagnosis was a significant adverse predictor for RFS (P = 0.028, HR: 1.979, 95%CI: 1.075–3.644). In multivariate analysis, we identified 2 trends towards independent prognostic factors for OS, including BM blasts at diagnosis (P = 0.057, HR: 1.676, 95%CI: 0.984–2.854) and mutation status of CEBPα (P = 0.064, HR: 4.173, 95%CI: 0.918–18.966). Our data indicated that older age, gender and a previous history of hematologic diseases resulted in lower complete remission rate (P = 0.012, 0.051 and 0.086, respectively). We further developed an easy scoring system for predicting prognosis and response to induction therapy in older AML patients. Patients who had lower scores showed significantly longer OS and RFS (P = 0.0006 and 0.1001, respectively) and higher CR rate (P = 0.014). Our research is limited by its retrospective nature and the results from our study need to be further validated by prospective randomized clinical trials.
, , H Sengeløv, M Severinsen, L S Friis, C W Marcher, I H Dufva
Leukemia, Volume 29, pp 548-555; doi:10.1038/leu.2014.234

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, , Luca Maurillo, , Federica Loscocco, Palma Manduzio, Giovanni Sparaventi, Sergio Amadori, Giuseppe Visani
Published: 1 December 2013
Expert Review of Hematology, Volume 6, pp 767-784; doi:10.1586/17474086.2013.858018

The publisher has not yet granted permission to display this abstract.
, Piera Angelillo, Antonella Carbone, Cira Riccardi
International Journal of Hematologic Oncology, Volume 2, pp 355-358; doi:10.2217/ijh.13.44

, Fabio Cruciani, , , Filippo Ballerini, Carlo Marani, Enrico De Astis, Sara Aquino, Micaela Bergamaschi, Laura Mitscheunig, et al.
Annals of Hematology, Volume 92, pp 1309-1318; doi:10.1007/s00277-013-1780-7

The publisher has not yet granted permission to display this abstract.
, Charles A Schiffer
Published: 15 February 2013
The Lancet, Volume 381, pp 484-495; doi:10.1016/s0140-6736(12)61727-9

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Mediterranean Journal of Hematology and Infectious Diseases, Volume 5; doi:10.4084/mjhid.2013.025

Abstract:
The treatment of acute myeloid leukemia in older patients is still object of controversies, because of considerable heterogeneity of patients and disease. Reluctance in administering conventional intensive chemotherapy relies on life-threatening complications induced by treatment in an often frail patient population. Nonetheless, while there is general consensus on the management of frail patients with supportive care only, a wide area of uncertainty remains for a considerable proportion of patients in whom treatment beyond support is feasible, with the aim of altering the natural history of the disease. Several predictive score have been proposed in order to prevent toxicity in absence of survival advantage, however in the daily practice patients’ and physician attitude do still have a major role in the final therapeutic decision.
Marcos Antonio Mauricio Scheiner, Flavia Da Cunha Vasconcelos, Roberta Matta, Reinaldo Dal Bello Figueira Jr., , Marcos Antonio Mauricio Scheiner, Flavia Da Cunha Vasconcelos, Roberta Matta, Reinaldo Dal Bello Figueira Jr.,
Journal of Cancer Research and Clinical Oncology, Volume 138, pp 959-969; doi:10.1007/s00432-012-1170-x

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Expert Opinion on Investigational Drugs, Volume 21, pp 179-189; doi:10.1517/13543784.2012.646082

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